The long range goals of this project are to determine the role of I-region associated (Ia) antigens in the regulation of immunocompetent cell interactions and to determine the mechanism of action and site of expression of the major histocompatibility complex (MHC) linked immune response (Ir) genes. During the past year we have concentrated our studies on several different areas. We have: 1) demonstrated the existence of T cells of responder origin that recognize antigen in association with nonresponder macrophages. This result is most consistent with theories of Ir gene function based on the concept of a hole in the T cell repertoire taking place during the induction of self-tolerance; 2) constructed autoreactive murine T cell hybridomas which should allow us to precisely analyze the role of Ia antigens in the syngeneic mixed leukocyte reaction; 3) obtained evidence for macrophage processing of antigen which may occur at a site on the macrophage cell surface; 4) developed a model for the transfer of specific transplantation tolerance following induction of T suppressor cells by splenic allografting.